A study led by a UT Health San Antonio physician and several collaborating researchers has linked higher levels of the hormone cortisol to memory deficits and reduced brain size in middle-aged people.

While other research has focused on the hormone’s role in memory and cognition, the new study is notable for its high number of participants — more than 2,200 — and the relatively young age of those involved, 48 years old on average.

The study found that people with higher levels of cortisol, which is tied to stress, performed more poorly on memory and cognition tests and showed evidence of brain shrinkage, even as they exhibited no symptoms.

“The emphasis of the effects of stress and of cortisol on the heart and on heart attacks has been very well-known and appreciated,” said Dr. Sudha Seshadri, a senior author on the study and director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “The impact on brain function and thinking is often less appreciated.”

The study was published Wednesday in the journal Neurology. Its research data, which included brain scans and information on participants’ performance of certain tasks, was culled from a subset of participants in the Framingham Heart Study, a long-term, multigenerational research initiative on which Seshadri is a senior investigator.

It is unclear whether higher cortisol levels directly led to the results or contributed to other conditions that impacted the brains of participants, Seshadri said. However, the association remained even after adjustment for other factors.

Individuals whose cognition was impacted did not have abnormally high levels of cortisol, Seshadri said. Participants in the top 30 percent of heightened cortisol had smaller brains, as well as subtle changes in the matter connecting the two halves of the brain, she said.

“Cortisol, which is a marker of stress, seems to have an adverse impact on brain structure and function. And that this impact is seen even for people in their 40s and 50s,” Seshadri said.

Seshadri worked on the study as part of a team of researchers from the National Heart, Lung, and Blood Institute, the Boston University School of Medicine, Harvard Medical School and the University of California, Davis, at Sacramento.

Harvard’s Dr. Justin B. Echouffo-Tcheugui, a lead author on the study, said the research further builds on an understanding of cortisol’s effects on the brain.

“Cortisol affects many different functions, so it is important to fully investigate how high levels of the hormone may affect the brain,” he said in a news release. “While other studies have examined cortisol and memory, we believe our large, community-based study is the first to explore, in middle-aged people, fasting blood cortisol levels and brain volume, as well as memory and thinking skills.”

Seshadri said she would like to research the matter further in Hispanic populations, since the study’s participants were largely of European ancestry.

The study’s findings point to an opportunity for people to adopt lifestyle changes earlier in life to reduce their stress levels, Seshadri said, such as exercising or getting an adequate amount of sleep.

Dr. Sudha Seshadri, director of the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at UT Health San Antonio, is the senior author on a cortisol stress study.

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